Professor Alan Budney has provided consultation to GW Pharmaceuticals. Dr. Allsop, Professor Copeland, and Dr. Norberg are currently carrying out an investigator driven clinical trial using materials donated by GW Pharmaceuticals. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials. All other authors report no competing interest exists.
Conceived and designed the experiments: DJA JC MMN AJB. Performed the experiments: DJA. Analyzed the data: DJA. Contributed reagents/materials/analysis tools: SF AM JL. Wrote the paper: DJA JC MN AJB.
Questions over the clinical significance of cannabis withdrawal have hindered its inclusion as a discrete cannabis induced psychiatric condition in the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). This study aims to quantify functional impairment to normal daily activities from cannabis withdrawal, and looks at the factors predicting functional impairment. In addition the study tests the influence of functional impairment from cannabis withdrawal on cannabis use during and after an abstinence attempt.
A volunteer sample of 49 non-treatment seeking cannabis users who met DSM-IV criteria for dependence provided daily withdrawal-related functional impairment scores during a one-week baseline phase and two weeks of monitored abstinence from cannabis with a one month follow up. Functional impairment from withdrawal symptoms was strongly associated with symptom severity (p = 0.0001). Participants with more severe cannabis dependence before the abstinence attempt reported greater functional impairment from cannabis withdrawal (p = 0.03). Relapse to cannabis use during the abstinence period was associated with greater functional impairment from a subset of withdrawal symptoms in high dependence users. Higher levels of functional impairment during the abstinence attempt predicted higher levels of cannabis use at one month follow up (p = 0.001).
Cannabis withdrawal is clinically significant because it is associated with functional impairment to normal daily activities, as well as relapse to cannabis use. Sample size in the relapse group was small and the use of a non-treatment seeking population requires findings to be replicated in clinical samples. Tailoring treatments to target withdrawal symptoms contributing to functional impairment during a quit attempt may improve treatment outcomes.
The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) requires that a mental health diagnosis “..causes clinically significant distress or impairment in social, occupational, or other important areas of functioning” (
The evidence-base for cannabis withdrawal
Research attempting to demonstrate the clinical significance of cannabis withdrawal has used two approaches: (a) linking withdrawal intensity to distress and/or substance use
Two studies have looked at the clinical significance of individual cannabis withdrawal symptoms using Likert scales to tease apart variation in the level of functional impairment. In a retrospective survey of adults who made a recent quit attempt, Budney et al. (2008)
This study tested in a non clinical sample of non-treatment seekers, (1) whether the level of functional impairment during abstinence is predicted by severity of dependence, or pre-quit attempt cannabis use levels, whilst controlling for age and gender, and (2) what the relationship is between the intensity of cannabis withdrawal symptoms and the level of associated functional impairment. In addition the study had the following exploratory aims: (a) to test the hypothesis that relapse to cannabis use is associated with greater levels of functional impairment from cannabis withdrawal symptoms, (b) to test the hypothesis that greater functional impairment during the abstinence attempt is predictive of a greater amount of cannabis consumed during a one month follow-up period, and (c) to test what factors predict time to relapse.
Current cannabis users who were not seeking treatment for their cannabis use were recruited from Sydney, Australia using a targeted postcard campaign (
A phone screening interview was used to collect demographics, cannabis dependence severity using the Severity of Dependence Scale (SDS)
An online version of the CWS
Not at all Moderately Extremely | Negative Impact on daily activity (0–10) | ||||||||||||
|
The only thing I could think about was smoking some cannabis | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had a headache | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had no appetite | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I felt nauseous (like vomiting) | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I felt nervous | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had some angry outbursts | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had mood swings | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I felt depressed | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I was easily irritated | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had been imagining being stoned | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I felt restless | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I woke up early | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had a stomach ache | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had nightmares and/or strange dreams | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
Life seemed like an uphill struggle | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I woke up sweating at night | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had trouble getting to sleep at night | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I felt physically tense | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | |
|
I had hot flashes | 0 | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 |
The following statements describe how you have felt over the last
Score by summing each items value to a maximum withdrawal score of 190 (you can derive two scores from the scale: one for withdrawal intensity and one for the negative impact of withdrawal – each separate score has a theoretical maximum of 190).
Reprinted from Drug and Alcohol Dependence, Vol 119, Allsop, D.J., Norberg, M.M., Copeland, J., Fu, S., Budney, A.J. The Cannabis Withdrawal Scale development: Patterns and predictors of cannabis withdrawal and distress, 123–129., Copyright (2011), with permission from Elsevier (License number 2872801116106).
The University of New South Wales Human Research Ethics Committee approved all procedures (Approval number: HREC 09152). Study participants filled out the CWS online daily during a one-week baseline “smoking as usual” period, and a two-week cannabis abstinence attempt. The cannabis abstinence attempt was supported with a one-hour psychological intervention and contingency management payments totalling AU$450 for adherence to study protocol, including the provision of urine samples indicating no cannabis use during the two week abstinence period. Participants in the study visited the research facility five times over the course of their involvement in the study: once at baseline, once after a week of smoking as usual, once after the first week of abstinence, and again at the end of the second week of abstinence. A final visit for follow-up interviews was performed one month after the end of the experimental abstinence period. Study procedures, including eligibility screening, and a full documentation of face to face interview schedules, the content of the 1 hour psychological intervention at the beginning of the quit attempt and monitoring of study adherence (including confirmation of cannabis abstinence) are described in a previous report
Descriptive statistics were reported as frequency and means with standard deviations and ranges (except where non-parametric analyses were performed, where continuous variables were described using medians and interquartile range). Analysis of Variance, Pearson Chi Square and Fishers exact test were used to compare clinical characteristics of: (1) participants who relapsed to those who didn't relapse, and (2) participants who were lost to follow up to those who were not lost to follow-up.
To explore whether the level of functional impairment could be predicted by cannabis use, severity of dependence, age or gender, a General Linear Mixed Model (GLMM) was constructed with total daily functional impairment scores (summed across all 19 valid items in a day) as the dependent variable. The dependent variable represents repeated measurements, and the GLMM allows explicit modelling of covariance between daily measures within individual subjects (using an autoregressive covariance structure of order 1). The model was constructed in a hierarchical manner, with the null model consisting of the intercept only. Step one explored the effect of time in abstinence on functional impairment scores, as abstinence represents the primary and most fundamental independent variable generating withdrawal phenomena. Step two added the non-cannabis use related covariates (age and gender) in order to ensure they are controlled for ahead of adding the cannabis use variables, which are the hypothesised drivers of withdrawal related functional impairment. Step three added cannabis-related variables (pre-quit cannabis use levels and scores on the SDS), to test their relative explanatory power having controlled for other variables. SDS scores were analysed as continuous variables as dichotomising loses valuable statistical information and power and obscures any nonlinearities between variables
As mixed-effects models do not generate traditional R2 values, the variance in withdrawal related functional impairment explained by the variables at each step of the model was estimated using a pseudo R2 calculated from the log likelihood ratios output from mixed models (termed R2LR)
In order to examine the relationship between withdrawal severity and functional impairment, it was determined that all other possible drivers of functional impairment should first be controlled for. Hence the full model from Aim 1, examining the predictors of functional impairment was retained, with the addition of a final step. In this final step, the effect of adding CWS symptom severity scores on the explained observed variance in functional impairment was examined.
To assess if participants who relapsed during the abstinence period had higher levels of impairment from cannabis withdrawal, each symptom's functional impairment score was analysed separately using a univariate approach. Rank transformed functional impairment scores were used as dependent variables in a series of non parametric two way repeated measures Analysis of Variance
Withdrawal symptoms significant in the univariate analyses were then entered as independent variables in a multivariate logistic regression
To test the impact of functional impairment during abstinence on levels of cannabis use at one-month follow up, a linear regression (Generalized Linear Model – GLM) was constructed with average weekly cannabis use at follow-up as the dependent variable. The independent predictor was the CWS sum total functional impairment score, calculated by averaging daily scores across the two-week abstinence period. Pre-study cannabis use levels and SDS scores were controlled for as covariates. CWS functional impairment data was normalized with a square root transformation (as the data had a long positive tail).
A Generalised Linear Model was used to analyse the time taken to relapse (in days) (dependent variable), with the average change in functional impairment scores between baseline and abstinence as the independent variable. The analysis controlled for age, gender, SDS scores and the mean weekly cannabis use prior to entering the study.
All analyses were carried out using SPSS version 20.
Of the 131 people phone screened forty-nine enrolled in the study (see
Total daily functional impairment scores for high and low SDS groups (horizontal lines are the average functional impairment scores rated during the baseline “smoking as usual” week for each SDS group). For the purposes of graphical demonstration, SDS group was assigned based on a clinically informed split at 8 or above for high dependent users
Variable | Dependent users (N = 49) |
Gender (% Male) | 67 |
Age (years) | 30 (Range: 18–57; SD 9.59) |
Age of first cannabis use (years) | 16.1 (Range: 11–28; SD 3.16) |
Age of transition to regular cannabis use (years) | 19.6 (Range: 14–40; SD 4.97) |
Cannabis Severity of Dependence Scale Score | 7.7 (Range: 3–15; SD 3.03) |
# SCID cannabis dependence criteria endorsed | 5.62 (Range: 3–7; SD 1.05) |
Amount of cannabis consumed in baseline ‘smoking as usual’ week (in grams) | 7.76 (Range: 1.04–43.86; SD 9.29) |
# days abstinent from cannabis in the previous 3 months | 0.45 (Range: 0–5; SD 0.94) |
Amount of cannabis consumed per week during the one month follow up period (in grams) | 2.81 grams (Range: 0–17, SD 3.1) |
# Cigarettes consumed per week in the baseline ‘smoking as usual’ week | 40.3 (Range: 0–150, SD 47.7) |
# Cigarettes consumed per week during the two weeks of cannabis abstinence | 54.02 (Range: 0–192, SD 57.4) |
The results of the model to identify factors predicting levels of functional impairment from cannabis withdrawal are listed in
Variable | F-value(Degrees of Freedom) | p-value | AIC |
Δ |
|
Total daily functional impairment score | |||||
Null model | 6767.04 | 0 | |||
Intercept | 32.45 (1,41.99) | 0.0001 | |||
Step 1 | 6686.83 | 0.089 | 0.089 | ||
Time in abstinence | 2.35(14,365.01) | 0.004 | |||
Step 2 | 6679.71 | 0.0008 | 0.097 | ||
Age | 0.69(1/40.01) | 0.41 | |||
Gender | 0.19(1,40.11) | 0.66 | |||
Step 3 | 6638.25 | 0.04 | 0.14 | ||
Cannabis Use (g/week) | 0.81(1/33.98) | 0.38 | |||
SDS Score | 4.95(1/34.39) | 0.03 | |||
Step 4 | 6164.36 | 0.37 | 0.51 | ||
Total severity of cannabis withdrawal | 671.16(1/776.907) | 0.0001 |
. Akaikes Information Criterion,
. Likelihood ratio based R2 approximation.
Adding withdrawal severity scores at step 4 of the “predictors of functional impairment” model (
Univariate statistics comparing the effects of functional impairment from each withdrawal symptom on chances of relapse are shown in
Withdrawal Symptom | No relapse (n = 20) | Relapse (n = 5) | Time (within subjects) | Relapse vs no relapse (between subjects) | Time×relapse (interaction) | |||||
BaselineMedian (IQR) | Abstinence Week 1 Median (IQR) | Baseline Median (IQR) | Abstinence Week 1 Median (IQR) | F(1,23) | P | F(1,23) | P | F(1,23) | P | |
I had trouble getting sleep | 1 (2) | 1.5 (4) | 0 (4.5) | 5 (5.5) | 3.72 | 0.07 | 0.43 | 0.51 | 8.38 | 0.008 |
I had no appetite | 0 (3.25) | 1 (3) | 1 (3.5) | 5 (0.75) | 3.53 | 0.07 | 2.5 | 0.13 | 7.95 | 0.01 |
I felt anxious | 1 (3.75) | 2 (5) | 0 (3) | 2.5 (6.75) | 3.52 | 0.07 | 0.03 | 0.87 | 7.93 | 0.01 |
Life felt like an uphill struggle | 1 (2.75) | 2 (3.75) | 0 (3.75) | 3 (6) | 3.13 | 0.09 | 0.05 | 0.83 | 7.04 | 0.01 |
I felt physically tense | 1 (2) | 2 (3) | 1.5 (2.5) | 4.5 (5.5) | 2.35 | 0.14 | 1.21 | 0.28 | 5.29 | 0.03 |
I had mood swings | 1 (2) | 1 (4) | 1 (0.34) | 3.5 (4.75) | 2.15 | 0.16 | 0.59 | 0.45 | 4.84 | 0.04 |
I felt depressed | 0.5 (1) | 1 (3) | 0 (3.75) | 3 (6) | 1.99 | 0.17 | 0.1 | 0.75 | 4.49 | 0.05 |
I felt nauseous (like vomiting) | 0 (0) | 0 (1) | 0.83 (0.36) | 0.57 (4.7) | 1.33 | 0.26 | 0.003 | 0.96 | 2.98 | 0.09 |
Total CWS functional impairment score | 16 (31.5) | 24 (46.75) | 24.5 (13.75) | 60 (62) | 0.91 | 0.35 | 2.04 | 0.17 | 2.04 | 0.17 |
I yawned a lot | 0 (1) | 0 (2) | 1 (2.25) | 1.5 (4.75) | 0.87 | 0.36 | 2.62 | 0.12 | 1.96 | 0.18 |
I was easily irritated | 1 (2.75) | 1.5 (4) | 1.5 (3.25) | 5 (5.2) | 0.83 | 0.37 | 2.76 | 0.11 | 1.88 | 0.19 |
I felt nervous | 0.5 (2) | 1 (3.75) | 0 (3) | 1 (6) | 0.8 | 0.38 | 0.002 | 0.97 | 1.81 | 0.19 |
I woke up early | 2 (3.75) | 1 (4) | 1 (3.5) | 2 (1.5) | 0.68 | 0.42 | 0.03 | 0.86 | 1.53 | 0.23 |
I felt worried | 1 (2) | 2 (3) | 0 (3) | 1.5 (7.5) | 0.65 | 0.43 | 0.13 | 0.72 | 1.45 | 0.24 |
Thinking about smoking | 1 (3.75) | 2.5 (4.5) | 3.5 (4.5) | 6.5 (5.5) | 0.61 | 0.44 | 4.06 | 0.06 | 1.37 | 0.25 |
I had some angry outbursts | 0 (2.75) | 1 (2.75) | 1 (0.75) | 3.5 (4.75) | 0.16 | 0.69 | 2.16 | 0.16 | 0.36 | 0.55 |
I had a stomach ache | 0 (0) | 0 (0.75) | 0 (0.75) | 0 (2.25) | 0.14 | 0.72 | 0.008 | 0.93 | 0.3 | 0.59 |
I felt tired | 2 (2.75) | 2 (2.75) | 3 (2.25) | 3 (3.5) | 0.13 | 0.73 | 1.9 | 0.19 | 0.29 | 0.59 |
Imagining being stoned | 0 (2) | 2 (4) | 2.5 (4.75) | 6 (7.25) | 0.13 | 0.73 | 3.08 | 0.09 | 0.29 | 0.59 |
I had hot flashes | 0 (0) | 0 (2.5) | 0 (0.75) | 0 (1.5) | 1.35 | 0.74 | 0.04 | 0.85 | 0.26 | 0.62 |
I had nightmares or strange dreams | 0 (0.75) | 0 (1) | 0 (0.12) | 0.2 (2.35) | 0.03 | 0.86 | 0.9 | 0.35 | 0.08 | 0.79 |
I had a headache | 0.5 (2) | 1 (1.75) | 0.5 (1.75) | 0.5 (4) | 0.007 | 0.94 | 0.05 | 0.83 | 0.02 | 0.91 |
I woke up sweating at night | 0 (0.75) | 1 (3.5) | 0.5 (4.75) | 3 (6.25) | 0.009 | 0.93 | 1.45 | 0.23 | 0.02 | 0.88 |
I felt restless | 1 (2.75) | 2 (3) | 3.5 (2.5) | 5 (6) | 0.007 | 0.94 | 3.61 | 0.07 | 0.02 | 0.9 |
Medians and Interquartile range (IQR) with results from a non parametric two way repeated measures ANOVA (using ranked data) comparing change in functional impairment between baseline and abstinence week 1, between people who relapsed to cannabis use during the two weeks of attempted abstinence and those who didn't. rANOVA results are presented for the main effect of relapse group, the main effect of time, and the interaction of time and relapse group. The table is sorted by the F-value from the rANOVA interaction result to reflect the relative order of withdrawal symptoms with respect to their association with relapse (e.g. items at the top of the table are those that are most associated with relapse when comparing functional impairment changes from baseline to week one of abstinence).
Withdrawal Symptom | No relapse (n = 16) | Relapse (n = 5) | Time (within subjects) | Relapse vs no relapse (between subjects) | Time×relapse (interaction) | |||||
BaselineMedian (IQR) | Abstinence Week 1 Median (IQR) | Baseline Median (IQR) | Abstinence Week 1 Median (IQR) | F(1,19) | P | F(1,19) | P | F(1,19) | P | |
I had mood swings | 0 (1) | 0.5 (2) | 0 (1) | 0 (0.5) | 0.57 | 0.46 | 0.59 | 0.45 | 2.08 | 0.17 |
I had hot flashes | 0 (0) | 0 (0) | 0 (0) | 0 (0) | 0 | 1 | 0 | 1 | 1.65 | 0.22 |
I felt restless | 0 (2) | 0.5 (1) | 1 (3) | 0 (2) | 0.43 | 0.52 | 0.07 | 0.79 | 1.56 | 0.23 |
I woke up early | 0 (1.75) | 0 (1) | 0 (2) | 0 (0.5) | 0.3 | 0.59 | 0.28 | 0.61 | 1.08 | 0.31 |
Imagining being stoned | 0.5 (2) | 0 (1) | 0 (1) | 0 (2.5) | 0.28 | 0.6 | 0.21 | 0.65 | 1.04 | 0.32 |
I was easily irritated | 0 (1) | 1 (2) | 1 (1.5) | 0 (2) | 0.24 | 0.63 | 0.06 | 0.81 | 0.87 | 0.36 |
I had trouble getting sleep | 0.5 (1) | 1 (2) | 0 (3) | 0 (2) | 0.22 | 0.65 | 0.22 | 0.65 | 0.79 | 0.39 |
I had some angry outbursts | 0 (1) | 1 (1.7) | 1 (1.5) | 0 (2.5) | 0.2 | 0.66 | 0.15 | 0.7 | 0.73 | 0.41 |
I felt anxious | 0 (2) | 0 (1) | 0 (1) | 0 (1.5) | 0.15 | 0.7 | 0.01 | 0.94 | 0.54 | 0.47 |
Thinking about smoking | 1 (2) | 1 (2) | 0 (1.5) | 0 (2.5) | 1.29 | 0.72 | 0.27 | 0.61 | 0.47 | 0.5 |
I had a stomach ache | 0 (1) | 0 (1) | 0 (0) | 0 (0.5) | 0.12 | 0.73 | 2.64 | 0.12 | 0.45 | 0.51 |
I woke up sweating at night | 0 (0) | 0 (0) | 0 (0.5) | 0 (1.5) | 0.11 | 0.74 | 0.33 | 0.58 | 0.41 | 0.53 |
I felt nervous | 0 (0.75) | 0 (1) | 0 (0.5) | 0 (1) | 0.1 | 0.75 | 0.01 | 0.91 | 0.38 | 0.55 |
Total CWS functional impairment score | 6 (11) | 12.5 (16) | 13 (15) | 8 (18) | 0.1 | 0.75 | 0.2 | 0.66 | 0.37 | 0.55 |
I had a headache | 0 (2.75) | 1 (1) | 0 (0.5) | 0 (0.5) | 0.1 | 0.76 | 2.08 | 0.17 | 0.35 | 0.56 |
I yawned a lot | 0 (1.75) | 0 (0) | 0 (1) | 0 (1) | 0.08 | 0.78 | 0.01 | 0.91 | 0.29 | 0.6 |
I had no appetite | 0 (1) | 0 (0.75) | 0 (2) | 0 (1) | 0.07 | 0.8 | 0 | 0.95 | 0.24 | 0.63 |
I felt depressed | 0 (1) | 0 (1) | 0 (0.21) | 0 (0.08) | 0.06 | 0.81 | 3.92 | 0.06 | 0.23 | 0.64 |
Life felt like an uphill struggle | 0 (1.75) | 0 (2) | 0 (0.5) | 0 (0.5) | 0.03 | 0.87 | 0.82 | 0.38 | 0.1 | 0.75 |
I felt worried | 0 (1) | 0.5 (1) | 0 (1) | 0 (2) | 0.02 | 0.89 | 0.2 | 0.66 | 0.07 | 0.79 |
I had nightmares or strange dreams | 0 0.75) | 0 (0) | 0 (0.5) | 0 (0.5) | 0.02 | 0.9 | 0.03 | 0.87 | 0.06 | 0.8 |
I felt tired | 2 (2.75) | 1.5 (3) | 2 (3) | 1 (2) | 0.02 | 0.9 | 1.26 | 0.28 | 0.05 | 0.82 |
I felt physically tense | 0 (1) | 0 (1) | 0 (1) | 0 (1.5) | 0.01 | 0.94 | 0 | 0.98 | 0.02 | 0.89 |
I felt nauseous (like vomiting) | 0 (0) | 0 (0.75) | 0 (0) | 0 (0.36) | 0.01 | 0.94 | 0.46 | 0.51 | 0.02 | 0.88 |
Medians and Interquartile range (IQR) with results from a non parametric two way repeated measures ANOVA (using ranked data) comparing change in functional impairment between baseline and abstinence week 1, between people who relapsed to cannabis use during the two weeks of attempted abstinence and those who didn't. rANOVA results are presented for the main effect of relapse group, the main effect of time, and the interaction of time and relapse group. The table is sorted by the F-value from the rANOVA interaction result to reflect the relative order of withdrawal symptoms with respect to their association with relapse (e.g. items at the top of the table are those that are most associated with relapse when comparing functional impairment changes from baseline to week one of abstinence).
The multivariate analysis used a logistic regression to test whether the withdrawal symptoms identified (above) as causing significant functional impairment in high SDS relapsers were predictive of relapse for the group as a whole. The omnibus tests in
Withdrawal measure | Wald/Omnibus Chi Sq | OR | OR 95% CI | |
|
8.525 | 0.036 | ||
I had trouble getting to sleep (abstinence – baseline) | 1.71 | 0.19 | 0.59 | 0.27, 1.29 |
I had no appetite (abstinence – baseline) | 0.93 | 0.33 | 1.38 | 0.71, 2.69 |
I felt physically tense (abstinence – baseline) | 4.4 | 0.036 | 2.52 | 1.06, 5.99 |
|
3.03 | 0.55 | ||
I felt anxious (abstinence – baseline) | 0.76 | 0.38 | 1.36 | 0.68, 2.75 |
Life felt like an uphill struggle (abstinence – baseline) | 0.03 | 0.87 | 1.08 | 0.42, 2.82 |
I had mood swings (abstinence – baseline) | 0.24 | 0.62 | 0.8 | 0.33, 1.93 |
I felt depressed (abstinence – baseline) | 0.35 | 0.55 | 1.38 | 0.47, 4.11 |
|
10.82 | 0.15 | ||
I had trouble getting to sleep (abstinence – baseline) | 1.98 | 0.16 | 0.58 | 0.27, 1.24 |
I had no appetite (abstinence – baseline) | 0.96 | 0.33 | 1.44 | 0.69, 3 |
I felt physically tense (abstinence – baseline) | 4.77 | 0.02 | 3.74 | 1.14, 12.19 |
I felt anxious (abstinence – baseline) | 0.05 | 0.83 | 1.1 | 0.46, 2.6 |
Life felt like an uphill struggle (abstinence – baseline) | 0.59 | 0.44 | 1.6 | 0.47, 5.7 |
I had mood swings (abstinence – baseline) | 1.7 | 0.19 | 0.47 | 0.15, 1.5 |
I felt depressed (abstinence – baseline) | 0.087 | 0.77 | 0.81 | 0.21, 3.2 |
As sample sizes are small in the relapse groups, a
The time to relapse variable was normally distributed amongst those who relapsed (Shapiro-Wilk (9) = 0.96, p = 0.8) but was not so when the full sample was considered (i.e. including people who succeeded in remaining abstinent for the full 14 days; Shapiro-Wilk (45) = 0.52, p = 0.0001). There was no difference in any of the following variables between those who relapsed and those who didn't: age (F1,45 = 1.69, p = 0.2, gender (Fishers exact test, p = 0.69), endorsement of SCID withdrawal dependence criteria (Fishers exact test, p = 0.7), the number of SCID dependence criteria endorsed (Pearson Chi Square = 0.83, p = 0.9), SDS score (F1,45 = 0.005, p = 0.94), or the amount of cannabis they smoked prior to entering the study (F1,45 = 0.031, p = 0.86). Functional impairment scores did not predict the number of days taken to relapse when controlling for age, gender, SDS score and pre-study cannabis use (F5, 41 = 0.56, p = 0.7).
To assess the relationship between functional impairment during abstinence and cannabis use during the one-month follow-up data were available for 40 of the 46 study participants. The six participants lost to follow up experienced significantly greater functional impairment from their withdrawal symptoms during the first week of abstinence (relative to baseline) than those who were followed up (week 1 mean total functional impairment increase for those lost to follow up = 26.8, mean increase for those who were able to be followed up = 6.8; F1, 45 = 6.6, p = 0.01), however the two groups of participants did not differ in their functional impairment scores during week 2 of abstinence (F1, 45 = 0.001, p = 0.97). Those lost to follow up were more likely to have relapsed: 40% (n = 4) of those who relapsed (n = 10) could not be followed up compared to only 5% (n = 2) of those who were able to maintain abstinence for the full two week period (n = 36) (Fishers exact test, p = 0.014). Those lost to follow up did not differ from the remaining 40 study participants in any of the following variables: age (F1,45 = 0.39, p = 0.53), gender (Fishers exact test, p = 0.65), SDS Score (F1, 45 = 0.48, p = 0.49), or the amount of cannabis they consumed prior to entering the study (F1,45 = 0.06, p = 0.8). Higher levels of functional impairment during the abstinence period significantly predicted higher levels of self-reported cannabis use at 1 month follow up (β = 0.019 (SE 0.39), t = 4.197, p = 0.0001), after controlling for baseline cannabis use levels (β = 0.025 (SE 0.01), t = 2.185, p = 0.029) and SDS scores (β = −0.19 (SE 0.06), t = −3.3, p = 0.001).
Consistent with previous work on withdrawal severity
Whilst the univariate analysis showed a subset of withdrawal symptoms were associated with increased functional impairment in those who relapsed (I had trouble getting to sleep, I had no appetite, I felt anxious, Life felt like an uphill struggle, I felt physically tense, I had mood swings and I felt depressed;
It is of note that the average level of functional impairment caused by cannabis withdrawal symptoms was relatively mild (the highest median total CWS functional impairment scores during abstinence were 60 out of a possible 190 during week 1 of abstinence in high SDS users who relapsed;
This study has several notable limitations. The sample size is small, which can lead to inflated Type I errors in the analyses, and precludes conduct of factor analyses on the CWS to test any
In conclusion, cannabis withdrawal is clinically significant because it is associated with elevated functional impairment to normal daily activities, and the more severe the withdrawal is, the more severe the functional impairment is. Elevated functional impairment from a cluster of cannabis withdrawal symptoms is associated with relapse in more severely dependent users. Those participants with higher levels of functional impairment from cannabis withdrawal also consumed more cannabis in the month following the end of the experimental abstinence period. Higher levels of cannabis dependence (scores on the SDS) predicted greater functional impairment from cannabis withdrawal. These findings suggest that higher SDS scores can be used to predict problematic withdrawal requiring more intense treatment that can be monitored closely using the Cannabis Withdrawal Scale (
Jennifer Mackenzie and Lisa Robins performed the Structured Clinical Interviews. John Saunders, Robert Ali and Michelle Dailey provided comments on the development of the study. Tim Slade, Barbara Toson, Mathew Crowther and Jennifer Chalmers provided statistical advice and discussion. David Burke helped prepare the images.